While multiple cardiovascular magnetic resonance (CMR) methods provide excellent reproducibility of global circumferential and global longitudinal strain, achieving highly reproducible segmental strain is more challenging. Previous single-center studies have demonstrated excellent reproducibility of displacement encoding with stimulated echoes (DENSE) segmental circumferential strain. The present study evaluated the reproducibility of DENSE for measurement of whole-slice or global circumferential (Ecc), longitudinal (Ell) and radial (Err) strain, torsion, and segmental Ecc at multiple centers. Six centers participated and a total of 81 subjects were studied, including 60 healthy subjects and 21 patients with various types of heart disease. CMR utilized 3 T scanners, and cine DENSE images were acquired in three short-axis planes and in the four-chamber long-axis view. During one imaging session, each subject underwent two separate DENSE scans to assess inter-scan reproducibility. Each subject was taken out of the scanner and repositioned between the scans. Intra-user, inter-user-same-site, inter-user-different-site, and inter-user-Human-Deep-Learning (DL) comparisons assessed the reproducibility of different users analyzing the same data. Inter-scan comparisons assessed the reproducibility of DENSE from scan to scan. The reproducibility of whole-slice or global Ecc, Ell and Err, torsion, and segmental Ecc were quantified using Bland–Altman analysis, the coefficient of variation (CV), and the intraclass correlation coefficient (ICC). CV was considered excellent for CV ≤ 10%, good for 10% < CV ≤ 20%, fair for 20% < CV ≤ 40%, and poor for CV > 40. ICC values were considered excellent for ICC > 0.74, good for ICC 0.6 < ICC ≤ 0.74, fair for ICC 0.4 < ICC ≤ 0.59, poor for ICC < 0.4. Based on CV and ICC, segmental Ecc provided excellent intra-user, inter-user-same-site, inter-user-different-site, inter-user-Human-DL reproducibility and good–excellent inter-scan reproducibility. Whole-slice Ecc and global Ell provided excellent intra-user, inter-user-same-site, inter-user-different-site, inter-user-Human-DL and inter-scan reproducibility. The reproducibility of torsion was good–excellent for all comparisons. For whole-slice Err, CV was in the fair-good range, and ICC was in the good–excellent range. Multicenter data show that 3 T CMR DENSE provides highly reproducible whole-slice and segmental Ecc, global Ell, and torsion measurements in healthy subjects and heart disease patients.

Cardiovascular magnetic resonance (CMR) cine displacement encoding with stimulated echoes (DENSE) measures heart motion by encoding myocardial displacement into the signal phase, facilitating high accuracy and reproducibility of global and segmental myocardial strain and providing benefits in clinical performance. While conventional methods for strain analysis of DENSE images are faster than those for myocardial tagging, they still require manual user assistance. The present study developed and evaluated deep learning methods for fully-automatic DENSE strain analysis. Convolutional neural networks (CNNs) were developed and trained to (a) identify the left-ventricular (LV) epicardial and endocardial borders, (b) identify the anterior right-ventricular (RV)-LV insertion point, and (c) perform phase unwrapping. Subsequent conventional automatic steps were employed to compute strain. The networks were trained using 12,415 short-axis DENSE images from 45 healthy subjects and 19 heart disease patients and were tested using 10,510 images from 25 healthy subjects and 19 patients. Each individual CNN was evaluated, and the end-to-end fully-automatic deep learning pipeline was compared to conventional user-assisted DENSE analysis using linear correlation and Bland Altman analysis of circumferential strain. LV myocardial segmentation U-Nets achieved a DICE similarity coefficient of 0.87 ± 0.04, a Hausdorff distance of 2.7 ± 1.0 pixels, and a mean surface distance of 0.41 ± 0.29 pixels in comparison with manual LV myocardial segmentation by an expert. The anterior RV-LV insertion point was detected within 1.38 ± 0.9 pixels compared to manually annotated data. The phase-unwrapping U-Net had similar or lower mean squared error vs. ground-truth data compared to the conventional path-following method for images with typical signal-to-noise ratio (SNR) or low SNR (p < 0.05), respectively. Bland–Altman analyses showed biases of 0.00 ± 0.03 and limits of agreement of − 0.04 to 0.05 or better for deep learning-based fully-automatic global and segmental end-systolic circumferential strain vs. conventional user-assisted methods. Deep learning enables fully-automatic global and segmental circumferential strain analysis of DENSE CMR providing excellent agreement with conventional user-assisted methods. Deep learning-based automatic strain analysis may facilitate greater clinical use of DENSE for the quantification of global and segmental strain in patients with cardiac disease.

Purpose: Myocardial strain is increasingly used to assess left ventricular (LV) function. Incorporation of LV deformation into finite element (FE) modeling environment with subsequent strain calculation will allow analysis to reach its full potential. We describe a new kinematic model-based analysis framework (KMAF) to calculate strain from 3D cine-DENSE (displacement encoding with stimulated echoes) MRI. Methods: Cine-DENSE allows measurement of 3D myocardial displacement with high spatial accuracy. The KMAF framework uses cine cardiovascular magnetic resonance (CMR) to facilitate cine-DENSE segmentation, interpolates cine-DENSE displacement, and kinematically deforms an FE model to calculate strain. This framework was validated in an axially compressed gel phantom and applied in 10 healthy sheep and 5 sheep after myocardial infarction (MI). Results: Excellent Bland-Altman agreement of peak circumferential (E-cc) and longitudinal (E-ll) strain (mean difference = 0.021 +/- 0.04 and -0.006 +/- 0.03, respectively), was found between KMAF estimates and idealized FE simulation. E-rr had a mean difference of -0.014 but larger variation (+/- 0.12). Cine-DENSE estimated end-systolic (ES) E-cc, E-ll and E-rr exhibited significant spatial variation for healthy sheep. Displacement magnitude was reduced on average by 27%, 42%, and 56% after MI in the remote, adjacent and MI regions, respectively. Conclusions: The KMAF framework allows accurate calculation of 3D LV Ecc and Ell from cine-DENSE.

OBJECTIVES The objective was to determine the feasibility and effectiveness of cardiac magnetic resonance (CMR) cine and strain imaging before and after cardiac resynchronization therapy (CRT) for assessment of response and the optimal resynchronization pacing strategy. BACKGROUND CMR with cardiac implantable electronic devices can safely provide high-quality right ventricular/left ventricular (LV) ejection fraction (RVEF/LVEF) assessments and strain. METHODS CMR with cine imaging, displacement encoding with stimulated echoes for the circumferential uniformity ratio estimate with singular value decomposition (CURE-SVD) dyssynchrony parameter, and scar assessment was performed before and after CRT. Whereas the pre-CRT scan constituted a single "imaging set" with complete volumetric, strain, and scar imaging, multiple imaging sets with complete strain and volumetric data were obtained during the post CRT scan for biventricular pacing (BIVP), LV pacing (LVP), and asynchronous atrial pacing modes by reprogramming the device outside the scanner between imaging sets. RESULTS 100 CMRs with a total of 162 imaging sets were performed in 50 patients (median age 70 years [IQR: 50-86 years]; 48% female). Reduction in LV end-diastolic volumes (P = 0.002) independent of CRT pacing were more prominent than corresponding reductions in right ventricular end-diastolic volumes (P = 0.16). A clear dependence of the optimal CRT pacing mode (BIVP vs LVP) on the PR interval (P = 0.0006) was demonstrated. The LVEF and RVEF improved more with BIVP than LVP with PR intervals $240 milliseconds (P = 0.025 and P = 0.002, respectively); the optimal mode (BIVP vs LVP) was variable with PR intervals <240 milliseconds. A lower pre-CRT displacement encoding with stimulated echoes (DENSE) CURE-SVD was associated with greater improvements in the post-CRT CURE-SVD (r =-0.69; P < 0.001), LV end-systolic volume (r =-0.58; P < 0.001), and LVEF (r =-0.52; P < 0.001). CONCLUSIONS CMR evaluation with assessment of multiple pacing modes during a single scan after CRT is feasible and provides useful information for patient care with respect to response and the optimal pacing strategy. (J Am Coll Cardiol Img 2021;14:2369-2383) (c) 2021 by the American College of Cardiology Foundation.

BackgroundSegmental extent of infarction assessed by late gadolinium enhancement (LGE) imaging early post‐ST‐segment elevation myocardial infarction (STEMI) has utility in predicting left ventricular functional recovery.HypothesisWe hypothesized that segmental circumferential strain with displacement encoding with stimulated echoes (DENSE) would be a stronger predictor of infarct transmurality than feature‐tracking strain, and noninferior to extracellular volume fraction (ECV).Study TypeProspective.PopulationFifty participants (mean ± SD, 59 ± 9 years, 40 [80%] male) underwent cardiac MRI on day 1 post‐STEMI.Field‐Strength/Sequences1.5T/cine, DENSE, T1 mapping, ECV, LGE.AssessmentTwo observers assessed segmental percentage LGE extent, presence of microvascular obstruction (MVO), circumferential and radial strain with DENSE and feature‐tracking, T1 relaxation times, and ECV.Statistical TestsNormality was tested using the Shapiro–Wilk test. Skewed distributions were analyzed utilizing Mann–Whitney or Kruskal–Wallis tests and normal distributed data using independent t‐tests. Diagnostic cutoff values were identified using the Youden index. The difference in area under the curve was compared using the z‐statistic.ResultsSegmental circumferential strain with DENSE was associated with the extent of infarction ≥50% (AUC [95% CI], cutoff value = 0.9 [0.8, 0.9], −10%) similar to ECV (AUC = 0.8 [0.8, 0.9], 37%) (P = 0.117) and superior to feature‐tracking circumferential strain (AUC = 0.7[0.7, 0.8], −19%) (P < 0.05). For the detection of segmental infarction ≥75%, circumferential strain with DENSE (AUC = 0.9 [0.8, 0.9], −10%) was noninferior to ECV (AUC = 0.8 [0.7, 0.9], 42%) (P = 0.132) and superior to feature‐tracking (AUC = 0.7 [0.7, 0.8], −13%) (P < 0.05). For MVO detection, circumferential strain with DENSE (AUC = 0.8 [0.8, 0.9], −12%) was superior to ECV (AUC = 0.8 [0.7, 0.8] 34%) (P < 0.05) and feature‐tracking (AUC = 0.7 [0.6, 0.7] −21%) (P < 0.05).Data ConclusionCircumferential strain with DENSE is a functional measure of infarct severity and may remove the need for gadolinium contrast agents in some circumstances.Level of Evidence2Technical Efficacy Stage5 J. MAGN. RESON. IMAGING 2020;52:1722–1731.

Recent advances in cardiac magnetic resonance (CMR) imaging facilitate a more comprehensive assessment of left ventricular function after cardiac resynchronization therapy (CRT). We set out to determine mechanisms of remodeling post-CRT based on strain and volumetric changes. CRT patients had CMR

OBJECTIVES This study sought to determine if combining the Seattle Heart Failure Model (SHFM-D) and cardiac magnetic resonance (CMR) provides complementary prognostic data for patients with cardiac resynchronization therapy (CRT) defibrillators. BACKGROUND The SHFM-D is among the most widely used risk stratification models for overall survival in patients with heart failure and implantable cardioverter-defibrillators (ICDs), and CMR provides highly detailed information regarding cardiac structure and function. METHODS CMR Displacement Encoding with Stimulated Echoes (DENSE) strain imaging was used to generate the circumferential uniformity ratio estimate with singular value decomposition (CURE-SVD) circumferential strain dyssynchrony parameter, and the SHFM-D was determined from clinical parameters. Multivariable Cox proportional hazards regression was used to determine adjusted hazard ratios and time-dependent areas under the curve for the primary endpoint of death, heart transplantation, left ventricular assist device, or appropriate ICD therapies. RESULTS The cohort consisted of 100 patients (65.5 [interquartile range 57.7 to 72.7] years; 29% female), of whom 47% had the primary clinical endpoint and 18% had appropriate ICD therapies during a median follow-up of 5.3 years. CURE-SVD and the SHFM-D were independently associated with the primary endpoint (SHFM-D: hazard ratio: 1.47/SD; 95% confidence interval: 1.06 to 2.03; p = 0.02) (CURE-SVD: hazard ratio: 1.54/SD; 95% confidence interval: 1.12 to 2.11; p = 0.009). Furthermore, a favorable prognostic group (Group A, with CURE-SVD <0.60 and SHFM-D <0.70) comprising approximately one-third of the patients had a very low rate of appropriate ICD therapies (1.5% per year) and a greater (90%) 4-year survival compared with Group B (CURE-SVD >= 0.60 or SHFM-D >= 0.70) patients (p = 0.02). CURE-SVD with DENSE had a stronger correlation with CRT response (r = -0.57; p < 0.0001) than CURE-SVD with feature tracking (r = -0.28; p = 0.004). CONCLUSIONS A combined approach to risk stratification using CMR DENSE strain imaging and a widely used clinical risk model, the SHFM-D, proved to be effective in this cohort of patients referred for CRT defibrillators. The combined use of CMR and clinical risk models represents a promising and novel paradigm to inform prognosis and device selection in the future. (C) 2020 by the American College of Cardiology Foundation.

ObjectiveDevelop an accelerated cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance (CMR) sequence to enable clinically feasible myocardial strain evaluation in patients with dilated cardiomyopathy (DCM).Materials and methodsA spiral cine DENSE sequence was modified by limiting the field of view in two dimensions using in-plane slice-selective pulses in the stimulated echo. This reduced breath hold duration from 20RR to 14RR intervals. Following phantom and pilot studies, the feasibility of the sequence to assess peak radial, circumferential, and longitudinal strain was tested in control subjects (n=18) and then applied in DCM patients (n=29).ResultsDENSE acquisition was possible in all participants. Elements of the data were not analysable in 1 control (6%) and 4 DCM r(14%) subjects due to off-resonance or susceptibility artefacts and low signal-to-noise ratio. Peak radial, circumferential, short-axis contour strain and longitudinal strain was reduced in DCM patients (p<0.001 vs. controls) and strain measurements correlated with left ventricular ejection fraction (with circumferential strain r=-0.79, p<0.0001; with vertical long-axis strain r=-0.76, p<0.0001). All strain measurements had good inter-observer agreement (ICC>0.80), except peak radial strain.DiscussionWe demonstrate the feasibility of CMR strain assessment in healthy controls and DCM patients using an accelerated cine DENSE technique. This may facilitate integration of strain assessment into routine CMR studies.

Heart failure with preserved ejection fraction (HFpEF) is frequently accompanied by comorbidities and a systemic proinflammatory state, resulting in coronary microvascular dysfunction (CMD), as well as myocardial fibrosis. The purpose of this study is to examine the relation between myocardial perfusion reserve (MPR) and diffuse myocardial fibrosis in patients with HFpEF using cardiovascular magnetic resonance. A single center study was performed in 19 patients with clinical HFpEF and 15 healthy control subjects who underwent quantitative first-pass perfusion imaging to calculate global MPR. T1 mapping was used to assess fibrosis and to calculate extracellular volume. Spiral tine displacement encoded stimulated echo was used to calculate myocardial strain. Comprehensive 2D echocardiograms with speckle tracking, cardiopulmonary exercise testing, and brain natriuretic peptide levels were also obtained. In patients with HFpEF, mean left ventricular EF was 61 % +/- 9% and left ventricular mass index 45 +/- 12 g/m(2). Compared with controls, HFpEF patients had reduced global MPR (2.29 +/- 0.64 vs 3.38 +/- 0.76, p = 0.002) and VO2 max (16.5 +/- 6.8 vs 30.9 +/- 7.7 ml/kg min, p <0.001) whereas extracellular volume (0.29 +/- 0.04 vs 0.25 +/- 0.04, p = 0.02), pulmonary artery systolic pressure (35.4 +/- 13.7 vs 22.3 +/- 5.4 mm Hg, p = 0.004), and average E/e' (15.0 +/- 7.6 vs 8.6 +/- 2.0, p = 0.005) were increased. Displacement encoded stimulated echo peak systolic circumferential strain (p = 0.60) as well as echocardiographic derived global longitudinal strain (p = 0.07) were similar between both groups. The prevalence of CMD, defined as global MPR <2.5, in the HFpEF group was 69%. In conclusion, HFpEF patients have a high prevalence of CMD and diffuse fibrosis. These parameters may be useful clinical end points for future therapeutic trials. (C) 2019 Elsevier Inc. All rights reserved.

Objective: We hypothesized that Displacement Encoding with Stimulated Echoes (DENSE) and feature-tracking derived circumferential strain would provide incremental prognostic value over the extent of infarction for recovery of segmental myocardial function. Methods: Two hundred and sixty-one patients (mean age 59 years, 73% male) underwent MRI 2 days post-ST elevation myocardial infarction (STEMI) and 241 (92%) underwent repeat imaging 6 months later. The MRI protocol included cine, 2D-cine DENSE, T2 mapping and late enhancement. Wall motion scoring was assessed by 2-blinded observers and adjudicated by a third. (WMS: 1 = normal, 2 = hypokinetic, 3 = akinetic, 4 = dyskinetic). WMS improvement was defined as a decrease in WMS >= 1, and normalization where WMS = 1 on follow-up. Segmental circumferential strain was derived utilizing DENSE and feature-tracking. A generalized linear mixed model with random effect of subject was constructed and used to account for repeated sampling when investigating predictors of segmental myocardial improvement or normalization Results: At baseline and follow-up, 1416 segments had evaluable data for all parameters. Circumferential strain by DENSE (p < 0.001) and feature-tracking (p < 0.001), extent of oedema (p < 0.001), infarct size (p < 0.001), and microvascular obstruction (p < 0.001) were associates of both improvement and normalization of WMS. Circumferential strain provided incremental predictive value even after accounting for infarct size, extent of oedema and microvascular obstruction, for segmental improvement (DENSE: odds ratio, 95% confidence intervals: 1.08 per - 1% peak strain, 1.05-1.12, p < 0.001, feature-tracking: odds ratio, 95% confidence intervals: 1.05 per - 1% peak strain, 1.03-1.07, p < 0.001) and segmental normalization (DENSE: 1.08 per -1% peak strain, 1.04-1.12, p < 0.001, feature-tracking: 1.06 per -1% peak strain, 1.04-1.08, p < 0.001). Conclusions: Circumferential strain provides incremental prognostic value over segmental infarct size in patients post STEMI for predicting segmental improvement or normalization by wall-motion scoring.

To evaluate the importance of strain‐correcting stimulated echo acquisition mode echo‐planar imaging cardiac diffusion tensor imaging.

The purpose of this systematic review is to provide a clinically relevant, disease-based perspective on myocardial strain imaging in patients with acute myocardial infarction or stable ischemic heart disease. Cardiac magnetic resonance imaging uniquely integrates myocardial function with pathology. Therefore, this review focuses on strain imaging with cardiac magnetic resonance. We have specifically considered the relationships between left ventricular (LV) strain, infarct pathologies, and their associations with prognosis. A comprehensive literature review was conducted in accordance with the PRISMA guidelines. Publications were identified that (1) described the relationship between strain and infarct pathologies, (2) assessed the relationship between strain and subsequent LV outcomes, and (3) assessed the relationship between strain and health outcomes. In patients with acute myocardial infarction, circumferential strain predicts the recovery of LV systolic function in the longer term. The prognostic value of longitudinal strain is less certain. Strain differentiates between infarcted versus noninfarcted myocardium, even in patients with stable ischemic heart disease with preserved LV ejection fraction. Strain recovery is impaired in infarcted segments with intramyocardial hemorrhage or microvascular obstruction. There are practical limitations to measuring strain with cardiac magnetic resonance in the acute setting, and knowledge gaps, including the lack of data showing incremental value in clinical practice. Critically, studies of cardiac magnetic resonance strain imaging in patients with ischemic heart disease have been limited by sample size and design. Strain imaging has potential as a tool to assess for early or subclinical changes in LV function, and strain is now being included as a surrogate measure of outcome in therapeutic trials.

PurposeTo image late mechanical activation and identify effective left‐ventricular (LV) pacing sites for cardiac resynchronization therapy (CRT). There is variability in defining mechanical activation time, with some studies using the time to peak strain (TPS) and some using the time to the onset of circumferential shortening (TOS). We developed improved methods for imaging mechanical activation and evaluated them in heart failure (HF) patients undergoing CRT.Materials and MethodsWe applied active contours to cine displacement encoding with stimulated echoes (DENSE) strain images to detect TOS. Six healthy volunteers underwent magnetic resonance imaging (MRI) at 1.5T, and 50 patients underwent pre‐CRT MRI (strain, scar, volumes) and echocardiography, assessment of the electrical activation time (Q‐LV) at the LV pacing site, and echocardiography assessment of LV reverse remodeling 6 months after CRT. TPS at the LV pacing site was also measured by DENSE.ResultsThe latest TOS was greater in HF patients vs. healthy subjects (112 ± 28 msec vs. 61 ± 7 msec, P < 0.01). The correlation between TOS and Q‐LV was strong (r > 0.75; P < 0.001) and better than between TPS and Q‐LV (r < 0.62; P ≥ 0.006). Twenty‐three of 50 patients had the latest activating segment in a region other than the mid‐ventricular lateral wall, the most common site for the CRT LV lead. Using a multivariable model, TOS/QRS was significantly associated with LV reverse remodeling even after adjustment for overall dyssynchrony and scar (P < 0.05), whereas TPS was not (P = 0.49).ConclusionLate activation by cine DENSE TOS analysis is associated with improved LV reverse remodeling with CRT and deserves further study as a tool to achieve optimal LV lead placement in CRT.Level of Evidence: 1Technical Efficacy: Stage 1J. MAGN. RESON. IMAGING 2017;46:887–896

Cine Displacement Encoding with Stimulated Echoes (DENSE) provides accurate quantitative imaging of cardiac mechanics with rapid displacement and strain analysis; however, image acquisition times are relatively long. Compressed sensing (CS) with parallel imaging (PI) can generally provide high-quality images recovered from data sampled below the Nyquist rate. The purposes of the present study were to develop CS-PI-accelerated acquisition and reconstruction methods for cine DENSE, to assess their accuracy for cardiac imaging using retrospective undersampling, and to demonstrate their feasibility for prospectively-accelerated 2D cine DENSE imaging in a single breathhold.

Background Post-processing methods have been developed to quantify myocardial strain from steady-state free-precession (SSFP) cine images. In the left ventricle (LV), global strain measurements from SSFP in healthy volunteers and in some types of heart disease compare favorably with myocardial tagging as a reference. We compared heart deformation analysis (HDA) of SSFP images and cine Displacement Encoding with Stimulated Echoes (DENSE) for the assessment of global and segmental circumferential strain (Ecc) and derivative indices in healthy volunteers and heart failure (HF) patients with left bundle branch block (LBBB).

Figure 1 (a) A strain matrix reveals pre-stretch and late activation of the lateral wall (red arrow) in a patient with heart failure and LBBB.An active contour (black line) detects the mechanical activation times for all LV segments.(b) The corresponding activation time map shows late activation of the anterolateral wall.

Assessment of diffuse right ventricular (RV) fibrosis is of particular interest in pulmonary hypertension (PH) and heart failure (HF). Current cardiovascular magnetic resonance (CMR) T1 mapping techniques such as Modified Look-Locker inversion recovery (MOLLI) imaging have limited resolution, but accelerated and navigator-gated Look-Locker imaging for cardiac T1 estimation (ANGIE) is a novel CMR sequence with spatial resolution suitable for T1 mapping of the RV. We tested the hypothesis that patients with PH would have significantly more RV fibrosis detected with MRI ANGIE compared with normal volunteers and patients having HF with reduced (LV) ejection fraction (HFrEF) without co-existing PH, independent of RV dilatation and dysfunction.